The influence of an experimental liver cirrhosis upon the metabolism of diazepam and imipramine hydrochloride in the rat

Abstract

1. When either diazepam or imipramine hydrochloride was administered orally to rats with thioacetamide-induced hepatic cirrhosis, the biliary and faecal elimination of metabolites was significantly decreased compared with that in normal animals. However, renal excretion of metabolites of diazepam or imipramine was increased in the liver-damaged rats. 2. Experiments in vitro showed that liver homogenates from cirrhotic rats metabolized diazepam or imipramine hydrochloride in qualitatively and quantitatively similar ways to those from normal rats. 3. Clearance of radioactivity from the blood following i.v. administration of either diazepam or imipramine hydrochloride was prolonged in animals with experimental cirrhosis.